April 12, 2011 -- "Babies, babies, babies." That's how Miranda and Josh Crawford now describe a typical day after their two sets of identical twins -- quadruplets in all -- joined their two-year-old sister in February.
After trying to get pregnant for more than a year, Miranda, 34, and Josh, 28, of Charlotte, N.C., turned to artificial insemination, and then in vitro fertilization, to have their first daughter. Doctors transferred two embryos into Miranda's uterus, and one survived. On March 17, 2009, Miranda gave birth to Baby Joslyn.
But Miranda, 34, and Josh, 28, both registered nurses, hoped to eventually expand their family over time to three or four children.
A year later, the couple sought out in vitro fertilization for a second time. Again, doctors transferred two embryos into Miranda's uterus, and, just six weeks into the pregnancy, doctors told the couple that they would be having twins.
But the ultrasound was fuzzy, and both the doctor and Miranda wanted to confirm how many babies were growing in her belly.
She returned to the hospital four days later. This time, the ultrasound was clear -- there were four hearts beating on the screen, not two.
"I was shocked, the doctor was shocked," Miranda said. "Never had that happened in his entire career."
Typically one or two embryos are inserted into a woman's uterus during one round of IVF. Even then, the patient has about a 60 percent chance of getting pregnant at all. But both embryos had split in Miranda's uterus to create two sets of identical twins.
"For a woman who is less than 35 years old, it is recommended that one or two embryos be transferred into the uterus during a fresh IVF cycle," said Dr. Jani Jensen, a physician in the department of reproductive endocrinology and infertility at Mayo Clinic. "In this case, it appears that the guidelines were correctly followed, but that lightning struck twice."
After shock, Miranda said fear stepped in. The couple was aware of the risk and complications that come with multiple births.
A Risky Pregnancy
"The whole pregnancy was scary," Miranda said. "I wasn't sure if I was going to have a miscarriage, and I was always thinking that I could go into preterm labor at any moment."
"We took it day by day," said Josh.
Rare Situation Surprises IVF Experts
"This is certainly an unusual outcome," Jensen said. "I've never seen it happen quite like this."
Jensen said she has rarely seen embryos split, but doctors estimate that it can happen in a little more than 1 percent of IVF cycles, and slightly more if the embryos are transferred as blastocysts, or embryos that have developed longer outside the body.
"The math here is mind-boggling: the patient likely only had about a 60 percent chance of getting pregnant at all, and with that, we expect that at least half of the time when two embryos are placed in the uterus, only one will continue to develop, so even twins are more of the exception, not the rule," Jensen said.
"To have both embryos implant and both undergo the rare phenomenon of splitting is extremely unusual," Jensen continued. "There are a few reports of this happening worldwide, but overall, it's a rarity."
Only 2 percent of all pregnancies result in one set of identical twins. Dr. James Grifo, director of the NYU Fertility Center, broke down the math.
"Embryo splitting occurs approximately in one out of 100 embryo transfers," Grifo said. "The chance of this outcome is approximately one in 10,000. This could also occur in a natural conception, but the chance of that is much [rarer].
"We have done around 20,000 IVF cycles and have fortunately not seen this outcome," he said. "It represents a very risky obstetrical situation, but it sounds like they were fortunate and had a good outcome."
"This is so rare, it is almost a record," said Dr. Michelle Warren, medical director for the Center for Menopause, Hormonal Disorders and Women's Health in New York. "However there is a view that only one embryo should be implanted at a time, particularly in patients with proven success. The issue is cost and if IVF wasn't so expensive, this would undoubtedly be standard of care."
One, No More Than Two Embryos
Warren said many European countries do not allow more than one embryo at a time because of the high risk and cost of multiple pregnancies, along with health problems with the babies.
Identical twins following IVF tend to share a placenta and one of the pregnancy membranes, which makes the twin pregnancy riskier in terms of harsh growth conditions and death in the womb for one of the twins.
The risk of preterm labor and delivery is very high with any sort of multiple births. Babies born premature are at an increased risk for many health complications, including learning disabilities, lung problems, cerebral palsy, blindness and deafness.
Because the pregnancy was so high-risk, doctors gave the Crawfords several options, including reduction, where one or some of the fetuses are aborted for the safety of the mother and the other growing babies.
The Crawfords said they never considered reduction.
Overall Healthy Pregnancy
Miranda developed gestational diabetes during the pregnancy, which she managed by controlling and restricting her diet.
"My sugars were very low, but it only lasted a little while," she said. "It worked itself out before the babies came."
She was also hospitalized twice in December when doctors feared she might go into preterm labor.
But for the circumstance, the couple said the pregnancy went very well, considering the risk.
Doctors put Miranda on strict bed rest in December. By the time she was ready to give birth, she had gained 60 pounds and her midsection measured in at five feet around.
"Even at 20 weeks, I looked like I was nine months pregnant," said Miranda. "I was huge."
Babies, Babies, Babies
Mia, Madison, Jackson and James were born on Feb. 4, 2010, 34 weeks into Miranda's pregnancy.
"They were all healthy, between four and a half and five and one-half pounds," Josh said.
The babies spent three weeks in the neonatal ICU so doctors could monitor their feeding toleration. By Feb. 28, the brood arrived at home, expanding the family of three to seven.
Five Babies: Teamwork
Miranda and Josh said that it's all about the teamwork when caring for the babies, and keeping the infants on the same eat-sleep rotation is key.
"They've gained the weight they've needed to gain, and now they can sleep as long as they want at night," Miranda said.
Usually, the babies are up every three to four hours. After their morning feeding, Miranda said she bathes them, gets them dressed, gives a second feeding, changes them for the afternoon and puts them in their sleepers at night.
Miranda breastfeeds two at a time while Josh bottle-feeds the other two babies. After having eight weeks off from work to care for the babies, Josh is back to work for the first time this week.
"I might not get a bath or get dressed, but the babies do," Miranda said.
"This case shows that nature is always ready to show doctors that we can't control everything," said Dr. Richard Paulson, professor of obstetrics and gynecology at the University of Southern California Keck School of Medicine. "As much as we try to avoid high-order multiple gestations by replacing fewer and fewer embryos, every once in a while, nature reminds us that we are not in charge."